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Purification and characterization of peptidases present in the venom of the scorpion Tityus serrulatus

Grant number: 13/15343-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): February 01, 2014
Effective date (End): August 31, 2017
Field of knowledge:Health Sciences - Collective Health - Public Health
Principal Investigator:Fernanda Calheta Vieira Portaro
Grantee:Daniela Cajado de Oliveira Souza Carvalho
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Accidents caused by scorpions represent a relevant issue for public health in Brazil, being more recurring than incidents with spiders and snakes. The main specie responsible for this situation is the scorpion Tityus serrulatus due to its reproductive strategy, the parthenogenesis, and the potential of its venom to induce severe clinical manifestations, even fatal, especially among children. In the composition of this venom, several neurotoxic peptides are described affecting Na + channels and K +, that are the main focus of studies. In contrast, little information is known about the other components of scorpion venom and its effects in the envenomation, especially related to the enzymatic components of this poison. Recent studies have shown the presence of peptidases in T. serrulatus's venom (TsV) and suggest a role in the formation of peptides, that are their most abundant components. Furthermore, our previously results showed that the metallopeptidases present in this venom are capable of hydrolize the neuropeptide dynorphin 1-13 in vitro releasing Leu-enkephalin, that can interact with ion channels and may promote an indirect neurotoxicity. This cleavage is probably a result of synergism of more than one enzyme and, in addition, this activity is not blocked by the commercial antivenoms. Thus, this project aims to seek in-depth information about the participation of these enzymes in the envenomation and also evaluate the potential neutralization of the commercial antivenoms produced by Butantan Institute. We intend purify the metallopeptidase(s) in TsV responsible for the Leu-enkephalin's releasing, to seek new substrates of biological importance and to characterize the in vivo metallopeptidase(s) activities. These characterizations, so far unpublished, may contribute to a better knowledge of venom and envenomation, and may provide relevant information to the sera production section from Butantan Institute.

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DUZZI, BRUNO; CAJADO-CARVALHO, DANIELA; KUNIYOSHI, ALEXANDRE KAZUO; KODAMA, ROBERTO TADASHI; GOZZO, FABIO CESAR; FIORAMONTE, MARIANA; TAMBOURGI, DENISE VILARINHO; PORTARO, FERNANDA VIEIRA; RIOLI, VANESSA. [des-Arg(1)]-Proctolin: A novel NEP-like enzyme inhibitor identified in Tityus serrulatus venom. Peptides, v. 80, p. 18-24, . (12/06677-0, 14/12976-5, 13/15343-0)
DUZZI, BRUNO; FERNANDES SILVA, CRISTIANE CASTILHO; KODAMA, ROBERTO TADASHI; CAJADO-CARVALHO, DANIELA; SQUAIELLA-BAPTISTAO, CARLA CRISTINA; VIEIRA PORTARO, FERNANDA CALHETA. New Insights into the Hypotensins from Tityus serrulatus Venom: Pro-Inflammatory and Vasopeptidases Modulation Activities. TOXINS, v. 13, n. 12, p. 13-pg., . (19/20832-7, 14/12976-5, 15/13124-5, 13/15343-0)
CARVALHO, DANIELA CAJADO; KUNIYOSHI, ALEXANDRE K.; KODAMA, ROBERTO T.; OLIVEIRA, ANA K.; SERRANO, SOLANGE M. T.; TAMBOURGI, DENISE V.; PORTARO, FERNANDA V.. Neuropeptide Y Family-Degrading Metallopeptidases in the Tityus serrulatus Venom Partially Blocked by Commercial Antivenoms. TOXICOLOGICAL SCIENCES, v. 142, n. 2, p. 418-426, . (12/06677-0, 13/15343-0)
CAJADO-CARVALHO, DANIELA; KUNIYOSHI, ALEXANDRE KAZUO; DUZZI, BRUNO; IWAI, LEO KEI; DE OLIVEIRA, URSULA CASTRO; MEIRELLES JUNQUEIRA DE AZEVEDO, INACIO DE LOIOLA; KODAMA, ROBERTO TADASHI; PORTARO, FERNANDA VIEIRA. Insights into the Hypertensive Effects of Tityus serrulatus Scorpion Venom: Purification of an Angiotensin-Converting Enzyme-Like Peptidase. TOXINS, v. 8, n. 12, . (13/15343-0, 15/15364-3)
CAJADO-CARVALHO, DANIELA; FERNANDES DA SILVA, CRISTIANE CASTILHO; KODAMA, ROBERTO TADASHI; CEOLIN MARIANO, DOUGLAS OSCAR; PIMENTA, DANIEL CARVALHO; DUZZI, BRUNO; KUNIYOSHI, ALEXANDRE KAZUO; PORTARO, FERNANDA VIEIRA. Purification and Biochemical Characterization of TsMS 3 and TsMS 4: Neuropeptide-Degrading Metallopeptidases in the Tityus serrulatus Venom. TOXINS, v. 11, n. 4, . (13/15343-0, 15/15364-3)
CAJADO-CARVALHO, DANIELA; GALVAO, JULIANA; KUNIYOSHI, ALEXANDRE K.; CARNEIRO, PATRICIA DOS SANTOS; PAES LEME, ADRIANA FRANCO; PAULETTI, BIANCA ALVES; MARENGO, ELIANA BLINI; PORTARO, FERNANDA V.. Tityus serrulatus Scorpion Venom: In Vitro Tests and Their Correlation with In Vivo Lethal Dose Assay. TOXINS, v. 9, n. 12, . (15/15364-3, 13/15344-7, 13/15343-0, 09/54067-3)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CARVALHO, Daniela Cajado de Oliveira Souza. Purification and characterization of peptidases from the venom of Tityus serrulatus scorpion.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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